- Email: [email protected]
Boron neutron capture therapy (BNCT) for glioblastoma 4 multiforme: A phase II study evaluating a prolonged high-dose of 5 boronophenylalanine (BPA) at the Studsvik facility in Sweden
288
Letters to the Editor / Radiotherapy and Oncology 88 (2008) 285–288
Received 19 March 2008; received in revised form 28 May 2008; accepted 29 May 2008; Available online 9 July 2008
0167-8140/$ - see front matter c 2008 Elsevier Ireland Ltd. All rights reserved. doi: 10.1016/j.radonc.2008.05.026
Boron neutron capture therapy (BNCT) for glioblastoma 4 multiforme: A phase II study evaluating a prolonged highdose of 5 boronophenylalanine (BPA) at the Studsvik facility in Sweden
reason for this was mainly due to the different opinion in evaluation of the results expressed by Dr. Stenstam and by official representatives for the former Studsvik Company. We still believe that the concept of BNCT is most interesting and a challenge to further evaluate. Development of more efficient boron carriers is needed and, by studying the pharmacokinetics of BPA, it has been demonstrated that the timing of neutron irradiation may not have been optimal [1]. The potential efficacy of BNCT has also been indicated in a recent study in the head and neck cancer [3]. However, even the greatest enthusiast must accept a thorough scientific and clinical evaluation.
References Dear Editor We, the authors of the publication of the Swedish BNCTphase II study, as well as Britta Stenstam, former co-author and responsible physician employed to run the BNCT treatment of glioblastoma at the Studsvik BNCT facility, were disappointed when the results of our study were delivered by the independent CRO (clinical trial research organisation)/statistician engaged. Nevertheless, as scientists and clinicians we have to face the hard fact that time-to-tumour progression was only 5.8 months following treatment. This is very similar to what recently has been reported from another Swedish multicenter study in a similar study population, where the time to progress after conventional radiotherapy in glioblastoma was 5.1 months [2]. Therefore, it is our strong opinion that the conclusion ‘‘the efficacy of BNCT in the present protocol seems to be comparable with conventional radiotherapy’’ is correct. As stated in the study protocol, and clearly reported in the present paper, the treatment at relapse was to the discretion of each responsible physician. When retrospectively reviewing the information on the treatment at relapse, it was found that the patients had been given additional treatments. Among those, 13 patients (45%) had been treated with temozolomide and they had a substantial longer survival than those that did not receive temozolomide (17.7 vs. 11.5 months). Despite the fact that the groups were not comparable we believe that it should be misleading not to report this circumstance that, if not reported, could lead to the false impression that BNCT alone was the reason for the overall survival of 14.2 months from treatment. However, as we stated in the discussion ‘‘our results must be evaluated cautiously due to the risk of selections bias’’. We also regret that we have not been able to publish the results from the Swedish BNCT study earlier. However, the
[1] Bergenheim AT, Capala J, Roslin M, Henriksson R. Distribution of P-BPA and metabolic assessment in glioblastoma. A microdialysis study in patients during BNCT treatment. J NeuroOncology 2005;71:287–93. [2] Henriksson R, Malmstro ¨m A, Bergh G, Trojanowsky T, Andreasson L, Blomquist E, et al. Highgrade astrocytoma concomitantly treated with estramustine and radiotherapy. J Neuro-Oncology 2006;78:321–6. [3] Kankaanranta L, Seppa ¨la ¨ T, Koivunoro H, Saarilahti K, Atula T, Collan J, et al. Boron neutron capture therapy in the treatment of locally recurred head and neck cancer. Int J Radiat Oncol Biol Phys 2007;69:475–82.
Roger Henriksson* Jacek Capala Annika Michanek ˚ ke Lindahl Sten-A Leif G. Salford Lars Franze ´n Erik Blomquist Jan-Erik Westlin Tommy Bergenheim University Hospital, Department of Radiation Sciences, Umea, Sweden E-mail address: [email protected]
*
Corresponding author.
Received 18 May 2008; accepted 18 May 2008; Available online 14 June 2008
0167-8140/$ - see front matter c 2008 Elsevier Ireland Ltd. All rights reserved. doi: 10.1016/j.radonc.2008.05.024
Letters to the Editor / Radiotherapy and Oncology 88 (2008) 285–288
Received 19 March 2008; received in revised form 28 May 2008; accepted 29 May 2008; Available online 9 July 2008
0167-8140/$ - see front matter c 2008 Elsevier Ireland Ltd. All rights reserved. doi: 10.1016/j.radonc.2008.05.026
Boron neutron capture therapy (BNCT) for glioblastoma 4 multiforme: A phase II study evaluating a prolonged highdose of 5 boronophenylalanine (BPA) at the Studsvik facility in Sweden
reason for this was mainly due to the different opinion in evaluation of the results expressed by Dr. Stenstam and by official representatives for the former Studsvik Company. We still believe that the concept of BNCT is most interesting and a challenge to further evaluate. Development of more efficient boron carriers is needed and, by studying the pharmacokinetics of BPA, it has been demonstrated that the timing of neutron irradiation may not have been optimal [1]. The potential efficacy of BNCT has also been indicated in a recent study in the head and neck cancer [3]. However, even the greatest enthusiast must accept a thorough scientific and clinical evaluation.
References Dear Editor We, the authors of the publication of the Swedish BNCTphase II study, as well as Britta Stenstam, former co-author and responsible physician employed to run the BNCT treatment of glioblastoma at the Studsvik BNCT facility, were disappointed when the results of our study were delivered by the independent CRO (clinical trial research organisation)/statistician engaged. Nevertheless, as scientists and clinicians we have to face the hard fact that time-to-tumour progression was only 5.8 months following treatment. This is very similar to what recently has been reported from another Swedish multicenter study in a similar study population, where the time to progress after conventional radiotherapy in glioblastoma was 5.1 months [2]. Therefore, it is our strong opinion that the conclusion ‘‘the efficacy of BNCT in the present protocol seems to be comparable with conventional radiotherapy’’ is correct. As stated in the study protocol, and clearly reported in the present paper, the treatment at relapse was to the discretion of each responsible physician. When retrospectively reviewing the information on the treatment at relapse, it was found that the patients had been given additional treatments. Among those, 13 patients (45%) had been treated with temozolomide and they had a substantial longer survival than those that did not receive temozolomide (17.7 vs. 11.5 months). Despite the fact that the groups were not comparable we believe that it should be misleading not to report this circumstance that, if not reported, could lead to the false impression that BNCT alone was the reason for the overall survival of 14.2 months from treatment. However, as we stated in the discussion ‘‘our results must be evaluated cautiously due to the risk of selections bias’’. We also regret that we have not been able to publish the results from the Swedish BNCT study earlier. However, the
[1] Bergenheim AT, Capala J, Roslin M, Henriksson R. Distribution of P-BPA and metabolic assessment in glioblastoma. A microdialysis study in patients during BNCT treatment. J NeuroOncology 2005;71:287–93. [2] Henriksson R, Malmstro ¨m A, Bergh G, Trojanowsky T, Andreasson L, Blomquist E, et al. Highgrade astrocytoma concomitantly treated with estramustine and radiotherapy. J Neuro-Oncology 2006;78:321–6. [3] Kankaanranta L, Seppa ¨la ¨ T, Koivunoro H, Saarilahti K, Atula T, Collan J, et al. Boron neutron capture therapy in the treatment of locally recurred head and neck cancer. Int J Radiat Oncol Biol Phys 2007;69:475–82.
Roger Henriksson* Jacek Capala Annika Michanek ˚ ke Lindahl Sten-A Leif G. Salford Lars Franze ´n Erik Blomquist Jan-Erik Westlin Tommy Bergenheim University Hospital, Department of Radiation Sciences, Umea, Sweden E-mail address: [email protected]
*
Corresponding author.
Received 18 May 2008; accepted 18 May 2008; Available online 14 June 2008
0167-8140/$ - see front matter c 2008 Elsevier Ireland Ltd. All rights reserved. doi: 10.1016/j.radonc.2008.05.024